Early detection of malignant neoplastic tissue is absolutely critical for successful treatment of many types of cancer. Various methods have been used to detect neoplastic tissue, but to date non-invasive methods of detecting such tissue have shown only limited usefulness. Many attempts have centered around discovering imaging agents which localize in neoplastic tissue.
There are materials such as certain porphyrins which do localize in neoplastic tissue. The porphyrins are complex tetrapyrrole compounds normally found in plants and animals. Many of these porphyrins fluoresce when exposed to an appropriate light source. One particular porphyrin preparation which selectively localizes in neoplastic tissue is hematoporphyrin derivative (HPD) prepared by treating hematoporphyrin with concentrated sulfuric acid, resulting in a crude mixture of several porphyrins. (Lipson et al J. Natl. Cancer Institute. 26:1-11, 1961) When injected into tumor bearing animals it localizes in tumors and produces a brilliant red-orange fluorescence when exposed to ultraviolet light. It has been found that dihematoporphyrin ether (DHE) (see formula I) is the active component of hematoporphyrin derivative responsible for tumor localizing properties.
Although HPD and DHE localize in neoplastic tissue and can be detected by photodynamic methods, the usefulness of these compounds is limited. This is primarily due to the fact that these photodynamic methods require invasive procedures. The HPD and DHE must be activated in situ by exposure to appropriate wavelength light. Direct observation of tissue fluorescence at best is qualitative and subjective, and varies widely between different investigators. Quenching of the fluorescence by normal tissue, body fluids, and blood is another major obstacle in achieving significant reliability and reproducibility in the use of this technique.
HPD has been radio labeled in an attempt to eliminate the major problems encountered by the photodynamic technique. Nuclear scintillation imaging procedures employing radio pharmaceuticals are simple and not invasive. Following parenteral administration of the radio labeled HPD, the radiopharmaceutical concentrates in the tumors to be detected and is imaged using appropriate nuclear medicine imaging devices. Past attempts have met with only limited success. Protoporphyrin and hematoporphyrin labeled with .sup.64 Cu were shown to concentrate in mouse tumors in vitro but failed to achieve significant tumor uptake in vivo. Similar results were obtained with .sup.57 Co-labeled hematoporphyrin. More recent studies indicate that .sup.99 Tc and .sup.111 In labeled compounds localize in neoplastic tissue but have no therapeutic value.